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SnET2 for the treatment of vascular disease: dose/response study in New Zealand white (NZW) rabbits

机译:SnET2治疗血管疾病:新西兰白兔的剂量/反应研究

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Abstract: Tin ethyl etiopurpurin, SnET2, is presently undergoing clinical trials for the treatment of cutaneous cancers and AIDS related Kaposi's sarcoma. Extensive pre-clinical work has been performed investigating the uptake, localization, and retention of SnET2 in catheter induced atheromatous plaques in New Zealand White (NZW) rabbits and juvenile female swine. The ultimate goal is to employ SnET2 for the prevention of intimal hyperplasia following various forms of angioplasty, thus enabling the prevention of a significant cause of restenosis. To that end, a dose/response study was undertaken to investigate the effect of varying total light dose (200, 100, and 50 J/cm$+2$/) and light dose rate (637, 318, 159 mW/cm$+2$/) during SnET2-Photodynamic Therapy, SnET2- PDT, of catheter induced plaque in a NZW rabbit iliac artery model. The SnET2 dose was held constant at 1.0 mg/kg b.w. and light was delivered intraluminally via a guidewire compatible light diffusing balloon catheter. The greatest light dose of those tested without inducing thermal damage was found to be 318 mW/cm$+2$/ while the total light dose of 50 J/cm$+2$/ produced PDT effect which was limited to the neo-intima. A relatively substantial total light dose of 200 J/cm$+2$/ was shown to produce a transmural PDT effect. This study demonstrated that the depth of PDT effect can be modulated by varying the total light dose.!15
机译:摘要:乙基乙基紫嘌呤锡SnET2目前正在临床试验中,用于治疗皮肤癌和艾滋病相关的卡波西氏肉瘤。已经进行了广泛的临床前研究,以研究SnET2在导管诱导的新西兰白兔和幼年雌性猪动脉粥样斑块中的摄取,定位和保留。最终目标是采用SnET2预防各种形式的血管成形术后的内膜增生,从而能够预防再狭窄的重要原因。为此,进行了剂量/响应研究,以研究变化的总光剂量(200、100和50 J / cm $ + 2 $ /)和光剂量率(637、318、159 mW / cm $在NZW兔动脉模型的导管诱发斑块的SnET2-光动力疗法SnET2-PDT期间,+ 2 $ /)。 SnET2剂量保持恒定在1.0mg / kgb.w。并通过与导丝兼容的光扩散球囊导管在腔内递送光。在不引起热损伤的情况下,测试的最大光剂量为318 mW / cm $ + 2 $ /,而总光剂量为50 J / cm $ + 2 $ /产生的PDT效果仅限于新内膜。 。相对较大的总光剂量为200 J / cm $ + 2 $ /被证明可产生透壁PDT效应。这项研究表明,PDT效应的深度可以通过改变总光剂量来调节。15

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